Brutkiewicz Randy R, Willard Claire A, Gillett-Heacock Kristin K, Pawlak M Robert, Bailey Jennifer C, Khan Masood A, Nagala Manjula, Du Wenjun, Gervay-Hague Jacquelyn, Renukaradhya Gourapura J
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Eur J Immunol. 2007 Sep;37(9):2390-5. doi: 10.1002/eji.200737124.
We have recently demonstrated that the p38 and ERK1/2 MAP kinases play reciprocal roles in the control of CD1d-mediated antigen presentation. Although the use of specific inhibitors for these pathways clearly had an effect, the effects were not complete, leading to speculations that additional pathways were involved. Here, we show that inhibiting protein kinase C delta (PKCdelta) substantially impairs antigen presentation by murine CD1d1 to NKT cells. This effect was accompanied by marked changes in the intracellular localization of CD1d. Expression of a dominant-negative mutant of PKCdelta in CD1d(+) cells resulted in nearly undetectable endogenous antigen presentation, substantially impaired CD1d recycling, a decrease in MAPK activation, and a decrease in the ability to present low (but not high) concentrations of alpha-galactosylceramide at the cell surface. These data strongly suggest that PKCdelta is a critical regulator of CD1d-mediated antigen presentation and is involved in multiple steps of the process.
我们最近证明，p38和ERK1/2丝裂原活化蛋白激酶在CD1d介导的抗原呈递控制中发挥相反作用。虽然使用这些途径的特异性抑制剂显然有效果，但效果并不完全，这引发了关于其他途径参与其中的猜测。在此，我们表明抑制蛋白激酶Cδ（PKCδ）会显著损害小鼠CD1d1向NKT细胞的抗原呈递。这种效应伴随着CD1d细胞内定位的显著变化。在CD1d(+)细胞中表达PKCδ的显性负性突变体导致几乎检测不到内源性抗原呈递，CD1d循环显著受损，丝裂原活化蛋白激酶（MAPK）激活减少，以及在细胞表面呈递低（但不是高）浓度α-半乳糖神经酰胺的能力下降。这些数据强烈表明，PKCδ是CD1d介导的抗原呈递的关键调节因子，并参与该过程的多个步骤。
